Harnessing diversity of Lactococcus lactis from raw goat milk: Design of an indigenous starter for the production of Rocamadour, a French PDO cheese.

Twenty-four strains of Lactococcus lactis isolated from raw goat milk collected in the Rocamadour PDO area were analysed by MLST typing and phenotypic characterisation. The strains were combined to design an indigenous starter for the production of Rocamadour PDO cheese. The strains were divided into three classes based on their technological properties: acidifying and proteolytic strains in class I (12/24 strains), slightly acidifying and non-proteolytic strains in class II (2/24 strains), and non-acidifying and non-proteolytic strains in class III (10/24 strains). Interestingly, all but three strains (21/24) produced diacetyl/acetoin despite not having citrate metabolism genes, as would classically be expected for the production of these aroma compounds. Three strains (EIP07A, EIP13D, and EIP20B) were selected for the indigenous starter based on the following inclusion/exclusion criteria: (i) no negative interactions between included strains, (ii) ability to metabolize lactose and at least one strain with the prtP gene and/or capable of producing diacetyl/acetoin, and (iii) selected strains derived from different farms to maximise genetic and phenotypic diversity. Despite consisting exclusively of L. lactis strains, the designed indigenous starter allowed reproducible cheese production with performances similar to those obtained with an industrial starter and with the sensory qualities expected of Rocamadour PDO cheese.

Circulating Tumor DNA Genomics Reveal Potential Mechanisms of Resistance to BRAF-Targeted Therapies in Patients with BRAF-Mutant Metastatic Non-Small Cell Lung Cancer.

PURPOSE: The limited knowledge on the molecular profile of patients with BRAF-mutant non-small cell lung cancer (NSCLC) who progress under BRAF-targeted therapies (BRAF-TT) has hampered the development of subsequent therapeutic strategies for these patients. Here, we evaluated the clinical utility of circulating tumor DNA (ctDNA)-targeted sequencing to identify canonical BRAF mutations and genomic alterations potentially related to resistance to BRAF-TT, in a large cohort of patients with BRAF-mutant NSCLC. EXPERIMENTAL DESIGN: This was a prospective study of 78 patients with advanced BRAF-mutant NSCLC, enrolled in 27 centers across France. Blood samples (n = 208) were collected from BRAF-TT-naïve patients (n = 47), patients nonprogressive under treatment (n = 115), or patients at disease progression (PD) to BRAF-TT (24/46 on BRAF monotherapy and 22/46 on BRAF/MEK combination therapy). ctDNA sequencing was performed using InVisionFirst-Lung. In silico structural modeling was used to predict the potential functional effect of the alterations found in ctDNA. RESULTS: BRAFV600E ctDNA was detected in 74% of BRAF-TT-naïve patients, where alterations in genes related with the MAPK and PI3K pathways, signal transducers, and protein kinases were identified in 29% of the samples. ctDNA positivity at the first radiographic evaluation under treatment, as well as BRAF-mutant ctDNA positivity at PD were associated with poor survival. Potential drivers of resistance to either BRAF-TT monotherapy or BRAF/MEK combination were identified in 46% of patients and these included activating mutations in effectors of the MAPK and PI3K pathways, as well as alterations in U2AF1, IDH1, and CTNNB1. CONCLUSIONS: ctDNA sequencing is clinically relevant for the detection of BRAF-activating mutations and the identification of alterations potentially related to resistance to BRAF-TT in BRAF-mutant NSCLC.

Twin-screw extrusion encapsulation of MCT-oil in a maltodextrin matrix using compatibilizing biopolymers.

Carbohydrates are the most recurrent materials employed for active components encapsulation using twin-screw extrusion. However, the influence of process parameters on the properties of the final product remains a challenge. In this paper, special attention was given to the incorporation of a hydrophobic model compound (MCT-oil), in a maltodextrin matrix with a compatibilizing biopolymer. The effects of the extrusion parameters, as well as the influence of different formulations were analyzed. The mild extrusion conditions allowed obtaining blends with acceptable texture and viscosity to enhance the dispersion of the active compound. The encapsulation systems obtained were in a glassy state at room temperature and they remained stable at 60 % RH for a long time. Satisfactory incorporation rates of MCT-oil were found reaching encapsulation efficiencies up to 90 %. These results showed that the chosen compatibilizing agent enhanced the dispersion and stabilization of the MCT-oil within the matrix and significantly improved encapsulation.

Prognostic role of a comprehensive geriatric assessment on the management of elderly patients with advanced non-small cell lung cancer (NSCLC): a pooled analysis of two prospective phase II trials by the GFPC Group.

BACKGROUND: The prognostic role of a comprehensive geriatric assessment (CGA) on the management of elderly patients with advanced-stage non-small cell lung cancer (NSCLC) remains to be established. The objective of this analysis was to determine the prognostic role of each CGA domain on overall survival (OS) among elderly patients with advanced-stage NSCLC. METHODS: We pooled individual data from two prospective, randomized phases II trials in patients over 65 years old with advanced-stage NSCLC, who were considered fit (0405 trial) or no-fit (0505 trial) based on a CGA. Both trials compared first-line chemotherapy followed by second-line erlotinib with the reverse strategy in terms of progression-free survival (PFS) and OS. Factors prognostic of OS were sought by using the Kaplan-Meier method and the log rank test for univariate analysis, and a Cox model for multivariate analysis. RESULTS: Analysis performed on 194 patients (mean age: 77 years, male gender: 70%, never- or ex-smokers: 56%) showed, in univariate analysis that performance status (PS), smoking status, Charlson, simplified Charlson, nutritional scores, and a mobility score were prognostics of OS. In multivariate analysis, PS [HR: 1.4 (1.02-1.9), P=0.04] and the Charlson score [HR: 1.46 (1.07-1.99), P=0.02] were independently prognostic of OS, while the nutritional score [HR: 0.69 (0.46-1.04), P=0.07] and the mobility score [HR: 0.25 (0.06-1.01), P=0.06] were close to significance. CONCLUSIONS: PS and comorbidities appear to be the main predictors of OS in elderly advanced NSCLC patients selected on the basis of CGA.

Antioxidant and Antimicrobial Activities of the Essential Oil of Achillea millefolium L. Grown in France.

Background: This study aimed to examine the composition of essential oil (EO) of A. millefolium aerial parts wild plant grown in France and evaluate its antioxidant, antibacterial, and antifungal activities. Methods: GC-MS was used to identify the chemical composition of EO. Antioxidant activity (AA) of EO was evaluated by Oxipres method. Antimicrobial activity of EO was evaluated by Agar-well diffusion and a broth microdilution assay. Results: Forty-three volatile compounds were identified. Major compounds were camphor (12.8%), germacrene-D (12%), (E)-nerolidol (7.3%), sabinene (6.7%), (E)-p-mentha-2,8-dien-1-ol (4.5%), and 1,8-cineole (4%). EO shows strong AA against Sunflower oil oxidation. Additionally, an inhibitory effect against microbial organisms (bacteria and fungi) was found. Conclusion: The EO composition of A. millefolium chemotype located in France was studied. The EO of the A. millefolium wild plant grown in France is quite an effective antioxidant in sunflower oil oxidation; it also possesses inhibitory effects against famous bacteria and fungi.

Evaluation and prevention of the negative matrix effect of terpenoids on pesticides in apples quantification by gas chromatography-tandem mass spectrometry.

The sample matrix can enhance the gas chromatography signal of pesticide residues relative to that obtained with the same concentration of pesticide in solvent. This paper is related to negative matrix effects observed in coupled gas chromatography-mass spectrometry ion trap (GC/MS2) quantification of pesticides in concentrated extracts of apple peel prepared by the Quick Easy Cheap Effective Rugged and Safe (QuEChERS) method. It is focused on the pesticides most frequently used on the apple varieties studied, throughout the crop cycle, right up to harvest, to combat pests and diseases and to improve fruit storage properties. Extracts from the fleshy receptacle (flesh), the epiderm (peel) and fruit of three apple varieties were studied by high-performance thin-layer chromatography hyphenated with UV-vis light detection (HPTLC/UV visible). The peel extracts had high concentrations of triterpenic acids (oleanolic and ursolic acids), reaching 25mgkg-1, whereas these compounds were not detected in the flesh extracts (<0.05mgkg-1). A significant relationship has been found between the levels of these molecules and negative matrix effects in GC/MS2. The differences in the behavior of pesticides with respect to matrix effects can be accounted for by the physicochemical characteristics of the molecules (lone pairs, labile hydrogen, conjugation). The HPTLC/UV visible method developed here for the characterization of QuEChERS extracts acts as a complementary clean-up method, aimed to decrease the negative matrix effects of such extracts.

Interactions between HIV infection and chronic obstructive pulmonary disease: Clinical and epidemiological aspects.

INTRODUCTION: An association between HIV infection and chronic obstructive pulmonary disease (COPD) has been observed in several studies. OBJECTIVE AND METHODS: we conducted a review of the literature linking HIV infection to COPD, focusing on clinical and epidemiological data published before and during widespread highly active antiretroviral therapy (HAART). RESULTS: Interactions between HIV infection and COPD appear to be influenced by multiple factors. In particular, the bronchopulmonary tract can be damaged by HIV infection, the immunodeficiency it induces, and the resulting increase in the risk of pulmonary infections. In addition, the prevalence of smoking and intravenous drug use is higher in HIV-infected populations, also increasing the risk of COPD. Before the advent of HAART, respiratory tract infections probably played a major role. Since the late 1990s and the widespread use of HAART, the frequency of opportunistic infections has fallen but new complications have emerged as life expectancy has increased. CONCLUSION: given the high prevalence of smoking among HIV-infected patients, COPD may contribute significantly to morbidity and mortality in this setting.

A totally thoracoscopic approach for pulmonary anatomic segmentectomies.

Reported experience with video-assisted anatomic pulmonary segmentectomy is still limited. Over a 28-month period, totally thoracoscopic (TT) anatomic segmentectomies, i.e. using only endoscopic instrumentation and video-display without utility incision, were attempted on 50 patients (25 males and 25 females), aged 18-81 years (mean: 57 years). The indication was a clinical N0 non-small cell lung carcinoma in 25 cases, a solitary metastasis in nine cases and a benign lesion in 16 cases. The following segmentectomies were performed: right apicosuperior (9) right superior (6), right basilar (7), lingula sparing left upper lobectomy (7), left apicosuperior (4), lingula (4), left superior (6) and left basilar (7). It was associated with a radical lymphadenectomy in 20 cases. There was one conversion to thoracotomy. The mean operative time was 188±54 min, the mean intraoperative blood loss was 91±82 ml (range: 0-450 ml). There were four minor postoperative complications (11.7%). The median postoperative stay was 5.6±2.4 days. Out of the 25 patients operated on for a cN0 lung carcinoma, two were finally upstaged to N2. TT anatomic pulmonary segmentectomies are feasible and safe.

Characterization of steam volatiles in the essential oil of black currant buds and the antioxidant properties of different bud extracts.

Currently essential oil from black currant ( Ribes nigrum L.) buds is mainly used as a valuable perfumery ingredient. This study reports more comprehensive characterization of dormant buds of various black currant ( Ribes nigrum L.) cultivars which are grown in Northern European countries. Essential oils were isolated from the buds by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS), GC-flame ionization detection (GC-FID), and GC--olfactometry (GC-O). The most abundant compounds in black currant bud essential oil were sabinene, delta-3-carene, and terpinolene. The most frequent descriptors of the essential oil components assessed by GC-O were "woody", "terpene", "fruity", "sweet", "citrus", "herbaceous", "pine", "green", "oily", "herbal", and "musty". The residues obtained after hydrodistillation were separated into liquid and solid fractions. The solid fraction was dried and extracted with acetone (AE), while the liquid fraction (water extract) was divided in two parts, one of which was spray-dried (SDWF extracts) and the other freeze-dried (FDWF extract). In addition, a portion of whole frozen buds was extracted with methanol (ME). The radical scavenging capacity (RSC) of black currant bud extracts varied in a wide range; in the DPPH * reaction system FDWF at the applied concentration scavenged 43-79%; SDWF, 54-80%; AE, 16-36%; ME, 42-60% of radicals; while in the ABTS *+ reaction system the RSC was 39-72, 38-53, 1-5, and 30-49%, respectively. The total amount of phenolic compounds expressed in gallic acid equivalents in FDWF varied in the range of 132-192 mg/g; in SDWF, 140-209 mg/g; in AE, 49-107 mg/g; and in ME extracts, 111-180 mg/g.

Impaired cortical processing of inspiratory loads in children with chronic respiratory defects.

BACKGROUND: Inspiratory occlusion evoked cortical potentials (the respiratory related-evoked potentials, RREPs) bear witness of the processing of changes in respiratory mechanics by the brain. Their impairment in children having suffered near-fatal asthma supports the hypothesis that relates asthma severity with the ability of the patients to perceive respiratory changes. It is not known whether or not chronic respiratory defects are associated with an alteration in brain processing of inspiratory loads. The aim of the present study was to compare the presence, the latencies and the amplitudes of the P1, N1, P2, and N2 components of the RREPs in children with chronic lung or neuromuscular disease. METHODS: RREPs were recorded in patients with stable asthma (n = 21), cystic fibrosis (n = 32), and neuromuscular disease (n = 16) and in healthy controls (n = 11). RESULTS: The 4 RREP components were significantly less frequently observed in the 3 groups of patients than in the controls. Within the patient groups, the N1 and the P2 components were significantly less frequently observed in the patients with asthma (16/21 for both components) and cystic fibrosis (20/32 and 14/32) than in the patients with neuromuscular disease (15/16 and 16/16). When present, the latencies and amplitudes of the 4 components were similar in the patients and controls. CONCLUSION: Chronic ventilatory defects in children are associated with an impaired cortical processing of afferent respiratory signals.